Mycobacterium tuberculosis, the causative agent of tuberculosis, remains one of the world's most successful and deadly infectious diseases. It is estimated by the World Health Organization that more than three million active cases of tuberculosis occur worldwide annually leading to greater than one million deaths. See World Health Organization, WHO Report 2007. HIV infected individuals are more prone to become infected with and develop the active form of the disease, and as the HIV pandemic has spread across the globe this has significantly contributed to the recent increase in the number of tuberculosis cases observed globally. See Centers for Disease Control, TB and HIV Coinfection, 2006. The currently recommend treatment for tuberculosis is a four drug regime for a minimum of six months that includes rifampin, isoniazid, pyrazinamide and ethambutol. This lengthy and burdensome regime leads to non-compliance by patients. This in turn has produced an increasing number of multidrug resistant (MDR) and extensively drug resistant (XDR) strains found in the clinic, for which effective therapeutic options are severely limited.
Accordingly, there is a clear need to develop new therapeutics to treat tuberculosis. In particular there is a need for anti-tuberculosis therapeutics that have, for example, potent anti-tuberculosis activity in vivo; activity against drug resistant tuberculosis strains, including MDR and XDR strains; excellent safety/low toxicity; no drug interactions or antagonism with other drugs commonly used to treat tuberculosis or HIV; activity against latent or slow growing bacteria to help reduce treatment time; and long serum half-lives to reduce dosing frequency.